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The investigator hypothesize that the combined use of (1) non-invasive biomarkers in peripheral blood predicting anti-donor immunological activation or quiescence (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive and induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients. It is therefore proposed an European, multicenter, prospective randomized comparing two strategies of follow-up: in the first, biopsies are guided by biomarkers, in the second one, a routine biopsy is performed at M3. In both groups, a biopsy is performed at M12 and whenever considered necessary by the clinician.
The main objective of this study is to demonstrate the ability of use of non-invasive biomarkers to decrease the number of allograft biopsies during the first year after transplantation. 300 new transplanted patients in the 7 clinical transplant sites will be included in the prospective multicentre EU-TRAIN Impact study with centralized storage of samples in CHUN (blood mRNA), ICS (blood cellular assays), Saint -Louis Hospital (blood anti-HLA DSA, and non-HLA antibodies), INSERM (Biopsy mRNA). Recruitment of patients will start on the day of transplantation (d-8 for transplantation from living donors) and data/samples collected over the first year following transplantation. Realization of all the acts for the research are representing the usual medical practice (Standard Of Care: SOC) except six additional blood samples that will be collected and analyzed specifically for the research and additional analysis done specifically for the research on half of one of the two biopsy cores from the recipient. 3 additional blood samples from the living donor will also be collected and analyzed specifically for the research (timepoint of the sampling: anytime from 8 days to the day of transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| routine group | No Intervention | Patients will follow a standard clinical follow-up based on kidney allograft function (serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and a surveillance allograft biopsies performed at 3 and 12 months after transplantation (M3 and M12). Visits with biopsies for clinical indication are left to the appreciation of the investigator | |
| biomarker guided follow-up | Experimental | Patients will follow a biomarker-guided strategy based on specific non-invasive biomarkers as defined in EUTRAIN-1 study on the basis of its detection and prediction capacities for rejection at M3 to decide whether a biopsy is performed. At M12 a routine biopsy is performed. Visits with biopsies for clinical indication are left to the appreciation of the investigator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| biomarker-guided strategy | Biological | Patients will follow a biomarker-guided strategy based on specific non-invasive biomarkers as defined in EUTRAIN-1 study on the basis of its detection and prediction capacities for rejection at M3 to decide whether a biopsy is performed. At M12 a routine biopsy is performed |
| Measure | Description | Time Frame |
|---|---|---|
| The rate of biopsies | comparison of the rate of biopsies performed during the first year in the Group of biomarkers guided biopsies vs. routine Group | up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of immunosuppressant treatment modifications | Rate of immunosuppressant treatment modifications in both groups. | 12month |
| Rate of complications due to performed biopsies | Rate of complications due to performed biopsies between both groups |
| Measure | Description | Time Frame |
|---|---|---|
| Safety endpoint | Comparison of The mean eGFR in both Groups estimated by glomerular filtration rate (CKD-EPI eGFR) at 12 months' post-transplantation and of the number of allograft rejection. | up to 12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexandre Loupy, Pr | APHP | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nantes Hospital | Nantes | 44000 | France | |||
| Saint-Louis Hospital, Paris |
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This is a 12-month follow-up multicenter, randomized, biomarker strategy design trial, whereby kidney transplant patients will be randomized 1:1 at the time of transplantation in 2 study groups:
In both groups, a biopsy can be performed up on clinical decision if needed.
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|
| 12month |
| Type of biopsy-proven rejections between both groups | Type of biopsy-proven rejections between both groups at 12 months after transplantation | 12month |
| Severity of biopsy-proven rejections between both groups | Severity of biopsy-proven rejections between both groups at 12 months after transplantation | 12month |
| Outcome of biopsy-proven rejections between both groups | Outcome of biopsy-proven rejections between both groups at 12 months after transplantation | 12month |
| Incidence of death | Incidence of death at 12 months after transplantation | 12 months |
| Incidence of allograft loss | Incidence of allograft loss at 12 months after transplantation | 12 months |
| Economic impact of implementing biomarkers in European Healthcare systems (cost/benefit) | Economic impact of implementing biomarkers in European Healthcare systems (cost/benefit) at 12 months after transplantation | up to 12 months |
| Health-related Quality of life (QoL) of transplant patients after receiving a user-friendly reporting format from the EU-TRAIN report. | Health-related Quality of life (QoL) of transplant patients after receiving a user-friendly reporting format from the EU-TRAIN report. | 12 months |
| Paris |
| Île-de-France Region |
| 75010 |
| France |
| Necker Hospital, Paris | Paris | Île-de-France Region | 75015 | France |
| Charité-Universitätsmedizin, Berlin | Berlin | 10117 | Germany |
| Charité-Universitätsmedizin, | Berlin | 10117 | Germany |
| Vall d'Hebron Hospital | Barcelona | 08035 | Spain |
| Bellvitge University Hospital | Barcelona | 08907 | Spain |
| Geneva University Hospitals | Geneva | Canton of Geneva | 1205 | Switzerland |